The objective of this proposal is to establish an NIEHS Center linking the University of Texas M.D. Anderson Cancer Center (UTMDACC), Science Park Campus and University of Texas at Austin (UTA) Campus. The primary objective of the proposed Environmental Health Sciences (EHS) Center is to study the mechanisms by which environment factors may cause or influence human disease and to develop methods for the detection, prevention and control of environmentally related diseases. Since most environmentally related diseases involve exposure to chemicals or physical factors, one major theme of this Center will be to develop and implement new methods to detect human exposure and/or to monitor disease prevention strategies. Furthermore, it is clear that genetic background plays a major role in the overall response to environmental exposures. Thus, another major theme of this Center will be to understand the genetic basis of variability in response to environmental exposure in humans through use of specific animal models as well as through studies in defined human populations, particularly underrepresented human populations. Because the problems of environment health are complex, requiring an understanding of the sources of chemical and physical stresses in the environment, their modes of transport and transformation, the routes of human exposure, the mechanisms through which the agents exert their effects, and the possible ways their actions may be influenced by modifiers or co-factors, including genetic background, the successful study of these complex problems required interdisciplinary approaches. To tackle this vast array of problems, the proposed Center will bring together, in an integrated effort, a multidisciplinary group of established scientists with an extremely broad range of expertise., In addition, the proposed center will provide these investigators access to sophisticated biochemical, molecular, and analytical techniques to enhance these research efforts. This Center will consist of 6 Research Cores: i) Mechanisms of Chemical Disposition and Toxicity; ii) Mechanisms of Neurotoxicity; iii) Mechanisms of DNA Damage and Mutagenesis; iv) Environmental Influences on Cell Growth and Differentiation; v) Environmental Epidemiology and Ecogenetics; and vi) Nutrition and Disease Prevention. The research efforts on these Research Cores will be enhanced by access to the following 6 Service Cores; i) Molecular Biology; ii) Transgenic Animals;; iii) Histology and Tissue Processing; iv) Flow Cytometry/Cell Elutriation; v) Analytical Instrumentation; and vi) Biostatistics and Data Processing. In addition, an Administrative Core will formalize collaborative interactions and provide for Enrichment Activities as well as a Pilot Project Program. Finally, a Community Outreach and Education Program will also establish a mechanism to disseminate important research findings of the Center to the general community, as well as provide community education programs with an emphasis on issues related to environmental health sciences.